tbuckley/cabot-search huggingface dataset:
Author Correction: A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC
Authors: Laurel B. Darragh, Michael M. Knitz, Junxiao Hu, Eric T. Clambey, Jennifer Backus, Andrew Dumit, Von Samedi, Andrew Bubak, Casey Greene, Timothy Waxweiler, Sanjana Mehrotra, Shilpa Bhatia, Jacob Gadwa, Thomas Bickett, Miles Piper, Kareem Fakhoury, Arthur Liu, Joshua Petit, Daniel Bowles, Ashesh Thaker, Kimberly Atiyeh, Julie Goddard, Robert Hoyer, Adrie Van Bokhoven, Kimberly Jordan, Antonio Jimeno, Angelo D’Alessandro, David Raben, Jessica D. McDermott, Sana D. Karam
Journal: Nature Cancer (2022)
Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization
Authors: Kevin R. Bersell, Tao Yang, Jonathan D. Mosley, Andrew M. Glazer, Andrew T. Hale, Dmytro O. Kryshtal, Kyungsoo Kim, Jeffrey D. Steimle, Jonathan D. Brown, Joe-Elie Salem, Courtney C. Campbell, Charles C. Hong, Quinn S. Wells, Amanda N. Johnson, Laura Short, Marcia A. Blair, Elijah R. Behr, Evmorfia Petropoulou, Yalda Jamshidi, Mark D. Benson, Michelle J. Keyes, Debby Ngo, Ramachandran S. Vasan, Qiong Yang, Robert E. Gerszten, Christian Shaffer, Shan Parikh, Quanhu Sheng, Prince J. Kannankeril, Ivan P. Moskowitz, John D. York, Thomas J. Wang, Bjorn C. Knollmann, Dan M. Roden
Journal: Circulation (2022)

Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene
Microenvironment‐Adaptive Nanozyme for Accelerating Drug‐Resistant Bacteria‐Infected Wound Healing
Authors: Lei Yu, Yiping Sun, Yusheng Niu, Pengfei Zhang, Jun Hu, Zhong Chen, Gong Zhang, Yuanhong Xu
Journal: Advanced Healthcare Materials (2022)

Reactive oxygen species (ROS) are favorable for antibacterial infection but their overproduction results in serious inflammatory response and aggravates the hypoxic state of the wound tissue, which is detrimental to healing stages of proliferation and remodeling. Here, an atomic-dispersion Fe-doped oxygen-deficient molybdenum oxide MoO3-X (ADFM) bifunctional nanozyme, featuring implanted peroxidase-like and enhanced catalase-like activity, is developed for decomposing H2 O2 into strongly oxidizing hydroxyl radicals (•OH) for prevention of bacterial infection and into plentiful O2 for healing stages. Therein, the introduction of Fe into MoO3-X primarily produces an asymmetric electron density difference by elongating the bond length between metal atoms, synchronously stabilizing adsorption of •OH and weakening the adsorption of O2 . ADFM also shows unimaginably high aqueous dispersity and pH-adaptive ROS regulation in the wound microenvironment, both of which are favorable for ADFM to fully exert enzyme-like activity for timely antibacterial and efficient wound-healing action. ADFM thus achieves efficient healing of drug-resistant bacteria-infected wounds in vivo, at an ultralow dosage of 30 µg mL-1 against 106 CFU mL-1 extended spectrum β-lactamases-producing Escherichia coli, exhibiting a wound-healing efficiency of ≈10 mm2 per day, which sets a benchmark among these noble-metal-free nanozyme-based wound-healing agents.
Discovery of a first-in-class orally available HBV cccDNA inhibitor
Authors: Li Wang, Qihui Zhu, Jitao David Zhang, Yaling Zhang, Xiaoju Ni, Kunlun Xiang, Jiaxi Jiang, Baocun Li, Youjun Yu, Hui Hu, Meifang Zhang, Waikwong Wu, Jing Zeng, Zhipeng Yan, Jieyu Dai, Kai Sun, Xin Zhang, Dongdong Chen, Song Feng, Lisa Sach-Peltason, John A.T. Young, Lu Gao
Journal: Journal of Hepatology (2022)
Increase in NDM-1 and NDM-1/OXA-48-producing Klebsiella pneumoniae in Germany associated with the war in Ukraine, 2022
Authors: Mirco Sandfort, Jörg B Hans, Martin A Fischer, Felix Reichert, Martina Cremanns, Jessica Eisfeld, Yvonne Pfeifer, Annika Heck, Tim Eckmanns, Guido Werner, Sören Gatermann, Sebastian Haller, Niels Pfennigwerth
Journal: Eurosurveillance (2022)

In 2022, German surveillance systems observed rapidly increasing numbers of NDM-1- and NDM-1/OXA-48-producing Klebsiella pneumoniae, which may in part reflect recurring pre-pandemic trends. Among these cases, however, a presence in Ukraine before diagnosis was frequently reported. Whole genome sequencing of 200 isolates showed a high prevalence of sequence types ST147, ST307, ST395 and ST23, including clusters corresponding to clonal dissemination and suggesting onward transmission in Germany. Screening and isolation of patients from Ukraine may help avoid onward transmission.
Hepatitis C time trends in reported cases and estimates of the hidden population born before 1965, Denmark and Sweden, 1990 to 2020
Authors: Peer Brehm Christensen, Birgit Debrabant, Susan Cowan, Kristian Debrabant, Anne Øvrehus, Ann-Sofi Duberg
Journal: Eurosurveillance (2022)

Background According to the World Health Organization, hepatitis C virus (HCV) infection should be under control by 2030. Aim Our aim was to describe the size and temporal changes in reported cases of chronic HCV infection in Denmark and Sweden and to estimate the size of the hidden (undiagnosed) population born before 1965. Methods We extracted all HCV infections reported to national surveillance systems in Denmark and Sweden from 1990 to 2020. Prediction of the size of the hidden HCV-infected population was restricted to the cohort born before 1965 and cases reported up to 2017. We applied a model based on removal sampling from binomial distributions, estimated the yearly probability of diagnosis, and deducted the original HCV-infected population size. Results Denmark (clinician-based) reported 10 times fewer hepatitis C cases annually than Sweden (laboratory and clinician-based), peaking in 2007 (n = 425) and 1992 (n = 4,537), respectively. In Denmark, the birth year distribution was monophasic with little change over time. In recent years, Sweden has had a bimodal birth year distribution, suggesting ongoing infection in the young population. In 2017, the total HCV-infected population born before 1965 was estimated at 10,737 living persons (95% confidence interval (CI): 9,744–11,806), including 5,054 undiagnosed, in Denmark and 16,124 (95% CI: 13,639–18,978), including 10,580 undiagnosed, in Sweden. Conclusions The reporting of HCV cases in Denmark and Sweden was different. For Denmark, the estimated hidden population was larger than the current national estimate, whereas in Sweden the estimate was in line with the latest published numbers.
Outcomes of post-exposure vaccination by modified vaccinia Ankara to prevent mpox (formerly monkeypox): a retrospective observational study in Lyon, France, June to August 2022
Authors: Yanis Merad, Alexandre Gaymard, Laurent Cotte, Thomas Perpoint, Dulce Alfaiate, Matthieu Godinot, Agathe Becker, Olivier Cannesson, Anne-Sophie Batalla, Fatima Oria-Yassir, Sophie Landré, Florence Morfin, Maude Bouscambert, Florent Valour, Florence Ader, Anne Conrad
Journal: Eurosurveillance (2022)

Modified vaccinia virus Ankara vaccine (MVA-BN; Bavarian Nordic) is recommended to contacts of mpox cases up to 14 days post-exposure but the effectiveness of this strategy is unknown. Among 108 adults (≥ 18 years old) who received one dose of MVA-BN after exposure to mpox, 11 (10%) cases of breakthrough mpox were observed. Sexual exposure was associated with the risk of breakthrough mpox (p = 0.0179). Samples taken from vaccinated breakthrough mpox cases had similar rates of infectious virus isolation than unvaccinated mpox cases.
Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022
Authors: Romy D Zwittink, Cornelia CH Wielders, Daan W Notermans, Nelianne J Verkaik, Annelot F Schoffelen, Sandra Witteveen, Varisha A Ganesh, Angela de Haan, Jeroen Bos, Jacinta Bakker, Caroline Schneeberger-van der Linden, Ed J Kuijper, Sabine C de Greeff, Antoni PA Hendrickx
Journal: Eurosurveillance (2022)

Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-β-lactamase (NDM) genes. Professionals should be aware of an increase in such MDRO associated with migration and medical evacuation of people from Ukraine.
Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 2022
Authors: Béatrice Berçot, François Caméléna, Manel Mérimèche, Susanne Jacobsson, Ghalia Sbaa, Mary Mainardis, Cyrille Valin, Jean-Michel Molina, Cécile Bébéar, Emilie Chazelle, Florence Lot, Daniel Golparian, Magnus Unemo
Journal: Eurosurveillance (2022)

We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC-199, and the novel mosaic penA-237.001 , which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001 , reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.
High caspase 3 and vulnerability to dual BCL2 family inhibition define ETO2::GLIS2 pediatric leukemia
Authors: Zakia Aid, Elie Robert, Cécile K. Lopez, Maxence Bourgoin, Fabien Boudia, Melchior Le Mene, Julie Riviere, Marie Baille, Salima Benbarche, Laurent Renou, Alexandre Fagnan, Cécile Thirant, Laetitia Federici, Laure Touchard, Yann Lecluse, Anton Jetten, Birgit Geoerger, Hélène Lapillonne, Eric Solary, Muriel Gaudry, Soheil Meshinchi, Françoise Pflumio, Patrick Auberger, Camille Lobry, Arnaud Petit, Arnaud Jacquel, Thomas Mercher
Journal: Leukemia (2022)
Wound healing dynamics, morbidity, and complications of palatal soft‐tissue harvesting
Authors: Lorenzo Tavelli, Shayan Barootchi, Martina Stefanini, Giovanni Zucchelli, William V. Giannobile, Hom‐Lay Wang
Journal: Periodontology 2000 (2022)

Abstract Palatal‐tissue harvesting is a routinely performed procedure in periodontal and peri‐implant plastic surgery. Over the years, several surgical approaches have been attempted with the aim of obtaining autogenous soft‐tissue grafts while minimizing patient morbidity, which is considered the most common drawback of palatal harvesting. At the same time, treatment errors during the procedure may increase not only postoperative discomfort or pain but also the risk of developing other complications, such as injury to the greater palatine artery, prolonged bleeding, wound/flap sloughing, necrosis, infection, and inadequate graft size or quality. This chapter described treatment errors and complications of palatal harvesting techniques, together with approaches for reducing patient morbidity and accelerating donor site wound healing. The role of biologic agents, photobiomodulation therapy, local and systemic factors, and genes implicated in palatal wound healing are also discussed.
Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines
Authors: Roy Hajjar, Emmanuel Gonzalez, Gabriela Fragoso, Manon Oliero, Ahmed Amine Alaoui, Annie Calvé, Hervé Vennin Rendos, Souad Djediai, Thibault Cuisiniere, Patrick Laplante, Claire Gerkins, Ayodeji Samuel Ajayi, Khoudia Diop, Nassima Taleb, Sophie Thérien, Frédéricke Schampaert, Hefzi Alratrout, François Dagbert, Rasmy Loungnarath, Herawaty Sebajang, Frank Schwenter, Ramses Wassef, Richard Ratelle, Eric Debroux, Jean-François Cailhier, Bertrand Routy, Borhane Annabi, Nicholas J B Brereton, Carole Richard, Manuela M Santos
Journal: Gut (2022)

Objective Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. Design The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo . Results Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii . Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. Conclusion Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.
Site of invasion revisited: epigenetic drivers of joint destruction in RA
Authors: Caroline Ospelt
Journal: Annals of the Rheumatic Diseases (2022)

New analytical methods and the increasing availability of synovial biopsies have recently provided unprecedented insights into synovial activation in general and synovial fibroblast (SF) biology in particular. In the course of this development, SFs have become one of the most rapidly evolving and exciting fields of rheumatoid arthritis (RA) research. While their active role in the invasion of RA synovium into cartilage has long been studied, recent studies have brought new aspects of their heterogeneity and propagation in RA. This review integrates old and new evidence to give an overview picture of the processes active at the sites of invasive synovial tissue growth in RA.
Sociodemographic Comparison of Children With High-risk Medical Conditions Referred vs Identified Through Screening Plus Outreach for COVID-19 Therapeutics
Authors: Simon Parzen-Johnson, Shan Sun, Ami B. Patel, Tonya L. Scardina, Seema K. Shah, Sameer J. Patel
Journal: JAMA Network Open (2022)

Minoritized groups are less likely to receive COVID-19 therapeutics, but few studies have identified potential methods to reduce disparities.
Single-cell transcriptome reveals dominant subgenome expression and transcriptional response to heat stress in Chinese cabbage
Authors: Xiaoxue Sun, Daling Feng, Mengyang Liu, Ruixin Qin, Yan Li, Yin Lu, Xiaomeng Zhang, Yanhua Wang, Shuxing Shen, Wei Ma, Jianjun Zhao
Journal: Genome biology (2022)

Abstract Background Chinese cabbage (Brassica rapa ssp. pekinensis) experienced a whole-genome triplication event and thus has three subgenomes: least fractioned, medium fractioned, and most fractioned subgenome. Environmental changes affect leaf development, which in turn influence the yield. To improve the yield and resistance to different climate scenarios, a comprehensive understanding of leaf development is required including insights into the full diversity of cell types and transcriptional networks underlying their specificity. Results Here, we generate the transcriptional landscape of Chinese cabbage leaf at single-cell resolution by performing single-cell RNA sequencing of 30,000 individual cells. We characterize seven major cell types with 19 transcriptionally distinct cell clusters based on the expression of the reported marker genes. We find that genes in the least fractioned subgenome are predominantly expressed compared with those in the medium and most fractioned subgenomes in different cell types. Moreover, we generate a single-cell transcriptional map of leaves in response to high temperature. We find that heat stress not only affects gene expression in a cell type-specific manner but also impacts subgenome dominance. Conclusions Our study highlights the transcriptional networks in different cell types and provides a better understanding of transcriptional regulation during leaf development and transcriptional response to heat stress in Chinese cabbage.
CircNTNG1 inhibits renal cell carcinoma progression via HOXA5-mediated epigenetic silencing of Slug
Authors: Yanping Liang, Junjie Cen, Yong Huang, Yong Fang, Yunfei Wang, Guannan Shu, Yihui Pan, Kangbo Huang, Jiaqi Dong, Mi Zhou, Yi Xu, Junhang Luo, Min Liu, Jiaxing Zhang
Journal: Molecular Cancer (2022)

Abstract Background Recent studies have identified that circular RNAs (circRNAs) have an important role in cancer via their well-recognized sponge effect on miRNAs, which regulates a large variety of cancer-related genes. However, only a few circRNAs have been well-studied in renal cell carcinoma (RCC) and their regulatory function remains largely elusive. Methods Bioinformatics approaches were used to characterize the differentially expressed circRNAs in our own circRNA-sequencing dataset, as well as two public circRNA microarray datasets. CircNTNG1 (hsa_circ_0002286) was identified as a potential tumor-suppressing circRNA. Transwell assay and CCK-8 assay were used to assess phenotypic changes. RNA pull-down, luciferase reporter assays and FISH experiment were used to confirm the interactions among circNTNG1, miR-19b-3p, and HOXA5 mRNA. GSEA was performed to explore the downstream pathway regulated by HOXA5. Immunoblotting, chromatin immunoprecipitation, and methylated DNA immunoprecipitation were used to study the mechanism of HOXA5. Results In all three circRNA datasets, circNTNG1, which was frequently deleted in RCC, showed significantly low expression in the tumor group. The basic properties of circNTNG1 were characterized, and phenotype studies also demonstrated the inhibitory effect of circNTNG1 on RCC cell aggressiveness. Clinically, circNTNG1 expression was associated with RCC stage and Fuhrman grade, and it also served as an independent predictive factor for both OS and RFS of RCC patients. Next, the sponge effect of circNTNG1 on miR-19b-3p and the inhibition of HOXA5 by miR-19b-3p were validated. GSEA analysis indicated that HOXA5 could inactivate the epithelial–mesenchymal transition (EMT) process, and this inactivation was mediated by HOXA5-induced SNAI2 (Slug) downregulation. Finally, it was confirmed that the Slug downregulation was caused by HOXA5, along with the DNA methyltransferase DNMT3A, binding to its promoter region and increasing the methylation level. Conclusions Based on the experimental data, in RCC, circNTNG1/miR-19b-3p/HOXA5 axis can regulate the epigenetic silencing of Slug, thus interfering EMT and metastasis of RCC. Together, our findings provide potential biomarkers and novel therapeutic targets for future study in RCC.
Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes
Authors: Dong Won Kim, Kevin J. Tu, Alice Wei, Ashley J. Lau, Anabel Gonzalez-Gil, Tianyu Cao, Kerstin Braunstein, Jonathan P. Ling, Juan C. Troncoso, Philip C. Wong, Seth Blackshaw, Ronald L. Schnaar, Tong Li
Journal: Molecular Neurodegeneration (2022)

Amongst risk alleles associated with late-onset Alzheimer's disease (AD), those that converged on the regulation of microglia activity have emerged as central to disease progression. Yet, how canonical amyloid-β (Aβ) and tau pathologies regulate microglia subtypes during the progression of AD remains poorly understood.We use single-cell RNA-sequencing to profile microglia subtypes from mice exhibiting both Aβ and tau pathologies across disease progression. We identify novel microglia subtypes that are induced in response to both Aβ and tau pathologies in a disease-stage-specific manner. To validate the observation in AD mouse models, we also generated a snRNA-Seq dataset from the human superior frontal gyrus (SFG) and entorhinal cortex (ERC) at different Braak stages.We show that during early-stage disease, interferon signaling induces a subtype of microglia termed Early-stage AD-Associated Microglia (EADAM) in response to both Aβ and tau pathologies. During late-stage disease, a second microglia subtype termed Late-stage AD-Associated Microglia (LADAM) is detected. While similar microglia subtypes are observed in other models of neurodegenerative disease, the magnitude and composition of gene signatures found in EADAM and LADAM are distinct, suggesting the necessity of both Aβ and tau pathologies to elicit their emergence. Importantly, the pattern of EADAM- and LADAM-associated gene expression is observed in microglia from AD brains, during the early (Braak II)- or late (Braak VI/V)- stage of the disease, respectively. Furthermore, we show that several Siglec genes are selectively expressed in either EADAM or LADAM. Siglecg is expressed in white-matter-associated LADAM, and expression of Siglec-10, the human orthologue of Siglecg, is progressively elevated in an AD-stage-dependent manner but not shown in non-AD tauopathy.Using scRNA-Seq in mouse models bearing amyloid-β and/or tau pathologies, we identify novel microglia subtypes induced by the combination of Aβ and tau pathologies in a disease stage-specific manner. Our findings suggest that both Aβ and tau pathologies are required for the disease stage-specific induction of EADAM and LADAM. In addition, we revealed Siglecs as biomarkers of AD progression and potential therapeutic targets.